Extended Huckel Molecular Orbital Calculations have been performed on 4-nitroquinoline-1-oxides (4-NQOs), the 4-hydroxylaminoquinoline-1- oxides (4-HAQOs) and on epoxides, lactones and aziridines. A model of the interaction of the 4-NQOs and 4-HAQOs with deoxyguanosine in DNA has been published which related carcinogenic activity to the strength of the charge transfer interaction between various 4-NQOs, nucleosides and DNA. The model of interaction of the 4-NQOs with DNA is being investigated integrating theoretical and experimental methods including spectrophotometric studies of base specificity, wavelength shifts and Benesi-Hilderbrand plots. The rate of conversion in vitro of an extensive series of 4-NQOs to the corresponding 4-HAQOs is under investigation. The 4-NQOs are being assayed for an accurate representation of relative carcinogenic activity. 100 MHz NMR is being utilized to clarify the occurrence of isomerism in the synthesis of various 4-NQOs. Frontier electron density indicates epoxide ring cleavage followed by electrophilic attack on guanosine by the carcinogenic epoxides. A large number of alkylated derivatives of guanosine have been produced in vivo and the rate of alkylation compared with carcinogenic activity. Carcinogenic epoxides have been shown to bond to guanosine in DNA in vivo while the non-carcinogenic are inactive. Similar studies have been carried out with beta- and gamma- lactones. A concept of decarboxylation and subsequent electrophilic attack by the carcinogenic gamma-lactones has been developed. The kinetics of alkylation, isolation and characterization of alkylated DNA and nucleosides are under investigation. The effect of various substituent groups on the carcinogenic activity of beta- and gamma- lactones and epoxides is being investigated. EHMO calculations have been performed on several monofunctional, difunctional and polyfunctional aziridines. There is a very high degree of correlation between the electrophilic activity of the ring carbons and carcinogenic activity. In vitro studies have resulted in N7-alkylation of guanosine derivatives by several aziridines.